Emollient, humectant, and fluorescent α,β-unsaturated thiol esters for long-acting skin applications

• Published in: Bioorganic chemistry 2008-12, Vol.36 (6), p.265-270
• Main Authors: Robinson, Carmen, Hartman, Rosemarie F., Rose, Seth D.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Amino Acids - chemistry; Catalysis; Chemistry, Organic - methods; Chloroform - chemistry; Conjugate addition; Cysteamine - chemistry; Emollients; Emollients - chemistry; Esters - chemistry; Fluorescent Dyes - chemistry; Humectants; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Michael-type addition; Models, Chemical; Moisturizers; Skin - drug effects; Skin - metabolism; Sulfhydryl Compounds - chemistry; Time Factors; α,β-Unsaturated thiol ester
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2008.06.004

α,β-Unsaturated thiol esters are subject to Michael-type addition by nucleophiles such as thiolates. Suitably substituted compounds may have utility as long-acting emollients (R = hydrophobic) or humectants (R = hydrophilic) by reaction with thiols in skin proteins. We describe compounds in which an emollient or a humectant bears an α,β-unsaturated thiol ester capable of reacting with nucleophilic amino acids in stratum corneum proteins. These compounds should serve as long-lasting moisturizers for skin. The emollient derivatized was octadecyl propanoate, and the humectant was poly(ethylene glycol). These hydrophobic and hydrophilic compounds, as well as a fluorescent, dansyl-containing thiol ester, were found to react within minutes with the thiol N-acetylcysteamine upon addition of a catalytic amount of an organic base in chloroform. The structures of the products resulting from conjugate addition to the unsaturated thiol esters were determined by NMR spectroscopy. In the case of the α,β,γ,δ-unsaturated (sorboyl) thiol ester, both the 1,4-addition product and the β,γ-unsaturated-1,6-addition product formed, followed by diadduct. An in vivo test of the fluorescent α,β-unsaturated thiol ester showed that this compound persisted on skin for 3 weeks vs. 6 days for the non-bonding control compound.